Fluid or medicament infusion programs are generally preferred to single or multiple injection programs in that the delivery rate of infusate can be controlled to a greater degree over a period of time. Typically, the infusate is topically administered directly onto the skin, wound site or eyes or is injected under the skin or directly into the vascular system or muscular tissue. In particular, continuous delivery parenteral drug therapy is most preferred because the controlled delivery of the medicament reduces toxic or other side effects associated with sharp pulses of the medicament, significantly improves the effectiveness of the therapy program, and increases patient comfort.
Broadly, an infusion device includes a container providing a reservoir of medicament or infusate coupled to a tube having a dispensing channel or the like. The tube includes a dispensing end which communicates directly with the recipient. Disposed in the fluid path between the dispensing end and the reservoir is a regulating device which controls the flow rate of the infusate through the channel.
The traditional and simplest infusion device for delivering sustained parenteral treatments is an intravenous drip apparatus which employs gravity to move the infusate from the reservoir through the channel and into the patient. The regulating device is often provided by a restrictor in the form of a roller clamp physically acting on an exterior surface of the tube which restricts the flow through the dispensing channel. One problem with these roller clamp restrictors, however, is that they are gravimetrically dependent on the hydrostatic pressure of the infusate formed at the roller clamp. Hence, the roller clamp cannot accurately regulate the dispensing flow because as the pressure head of the infusate decreases, the hydrostatic pressure decreases which proportionately reduces the flow rate of the infusate through the roller clamp.
To overcome this problem, electronic regulation devices were developed to replace the roller clamp restrictors. These electronic devices are capable of electronically sensing the flow rate through the channel and automatically adjusting the restriction area of flow through internal adjusters to maintain the desired infusion rate. While these devices have improved the accuracy of intravenous drip apparatus, they are burdensome and impractical since the dispensing reservoir must be positioned above the recipient at all times to create the proper pressure head at the electronic regulation device.
More advanced infusion systems have been developed which actively pump the infusate into the patient rather than relying on gravimetric infusion. Typically, a piston, plunger or the like is urged or advanced into a fixed volume dispensing reservoir containing the infusate which positively displaces the infusate and expels it from the reservoir. Examples of these infusion pumps include syringe pumps, reciprocating piston pumps and peristaltic pumps.
The driving forces displacing the piston or plunger are generally provided by spring elements, chemical systems or electric resources. The most common driving force, however, is that provided by an electric motor which is capable of controlling the infusate flow rate from the dispensing reservoir. Hence, the flow rate of the medicament or pharmaceutical agent suspended in the infusate can be customized to the particular needs of the patient more accurately than the intravenous drip apparatus.
While these above-mentioned intravenous drip apparatuses and infusion pumps are perfectly acceptable in a hospital environment, neither are ambulatory which severely restricts the activity of the recipient. Hence, considerable research has been devoted to the development of small disposable and portable infusion pumps of the positive displacement nature. Electronic powered delivery means or the like would provide a more selectable driving force to control the expulsion of the infusate from the dispensing reservoir but would not be suitable for a disposable product because of the inherent increased costs and weight. Therefore, these newly developed disposable infusion pumps generally utilize springs, vapor pressure or elastomeric balloons as a source of driving or displacement energy to expel the infusate from the dispensing reservoir. Due in part to the uncontrolled nature of these sources of driving energy, typically, a flow regulation internal restrictor is included in the fluid flow path between the infusion pump and the dispensing end. These restrictors are generally precision bore tubing elements or filter elements which impede the flow of the infusate through the fluid channel. Discrete value flow rate restrictors are available to incorporate in the fluid path to selectively establish infusate flow rate. Typical of these portable infusion pumps are disclosed in U.S. Pat. Nos. 4,201,207; 4,318,400; 4,386,929 and 4,597,758.
Presumably, these patented devices provide portability of the infusion pump and provide a range of discrete value restrictors to assure a proper selection of infusate flow rates. In practice, however, the flow rate cannot be precisely selected to suit the needs of a particular patient. Flow rate of the infusate is dependent on a number of factors such as the bore size of the restrictor and the fluid properties of the infusate. The bulk viscosity, for example, varies from fluid to fluid and is further dependent on the infusate's dispensing temperature. Moreover, infusates containing suspensions often cannot pass through the restrictors because the suspension particles become lodged in the bores or clog the filter elements. Accordingly, a wide range of discrete value restrictors as well as an astute knowledge of the infusate fluid properties must be made available to provide the desired flow rate for a particular infusate. Due to the economics and logistics, however, only the most common discrete value restrictors are produced and made widely available.
Osmotic infusion devices based on the Rose-Nelson pump principle have been developed which ar activated by imbibition of water (S. Rose and J. F. Nelson, "A Continuous long-Term Injector", Austral, J. exp Biol. 33, pp. 415-420 (1955)). A Rose-Nelson pump consists of three chambers: a salt chamber containing excess solid salt, an infusate chamber and a water chamber. The salt and water compartments are separated by a rigid semipermeable membrane permeable to water but impermeable to salt; the salt and infusate chambers are separated by a elastomeric diaphragm. As water is imbibed osmotically into the salt chamber, the salt chamber swells causing the elastomeric diaphragm to expand into the infusate chamber which forces the infusate therefrom through a delivery orifice. Examples of these osmotic infusion devices may be found in U.S. Pat. Nos. 3,604,417; 3,760,984; 3,845,770; 4,193,398; 4,474,575, 4,474,048; 4,552,561; and 4,838,862. Generally, the flow rate of the infusate of these devices is controlled by osmotic rate controllers which vary one or a combination of the: osmotic gradient, a function of the salt; and area of the semipermeable membrane as well as the membranes property characteristics.
However, similar to non-osmotic portable and disposable infusion pumps including discrete value internal restrictors, a variety of osmotic rate controllers must be available to suit the particular parenteral treatment needs of the patient. Again, because of economics and logistics, only the most common flow rates are provided for and made widely available.
Another form of drug dispensing is that provided by electrochemically driven drug dispensers. Generally, a first compartment is provided containing electrochemically active fluid molecules (in gas form). Disposed adjacent to the first compartment is a second compartment which is separated therefrom by an electrolytic membrane. An electrode contained in the first compartment acts as a catalyst in converting the fluid molecules in the first compartment to ions so that passage through the electrolytic membrane is permitted. An opposing electrode contained in the second compartment reconverts or recombines those ions back to fluid molecules in the second compartment. The net result is that fluid from the first compartment is recombined in the second compartment to fill the second compartment. The recombined fluid molecules create fluid pressure on an expandable diaphragm separating the second compartment from a drug containing chamber. In turn, the expanding diaphragm expels the drug from the chamber. Hence, the fluid pressure is determined by the magnitude of an electric current applied between the two opposing electrodes in conductive contact with the membrane and the diffusion rate through the membrane. Typical of these true electrochemically driven infusion devices may be found in U.S. Pat. Nos. 4,687,423 and 4,886,514.
While these devices may provide adequate dispensing of a drug under certain circumstances, some problems are inherent with these designs. In order to electrochemically convert the fluid molecule in the first compartment to an ion and then reconvert that ion back to a fluid molecule on the other side of the electrolytic membrane, a constant current must be applied between the electrodes. Hence, a power source is always required to provide this sustained current for the duration of the dispensing period. Moreover, since the fluid employed to drive the diaphragm is generally gaseous, it is highly susceptible to external environmental changes, such as temperature. Accordingly, the pressure exerted on the diaphragm may vary in these instances which ultimately change the rate of dispensing the drug. More recently, though still in its infancy, electrochemical controlled dispensing mechanisms for drug delivery have been developed. These infusion pumps, incorporating electrochemical mechanisms, generally include a layered composite of a microporous alumina membrane and a gold microporous electrode coated with an impermeable overlay barrier which spans and covers the micropores of the electrode. On one side of the composite is a dispensing reservoir of infusate in flow contact with the electrode and the barrier which prevents the infusate from flowing through the micropores and into a dispensing channel. Hence, by opening the barrier layer covering the electrode micropores, the infusate is permitted to pass through the layered composite and into the recipient via the dispensing channel (M. J. Tierney and C. R. Martin, "Electrorelease Systems Based on Microporous Membranes", J. Electrochem. Soc. Vol. 137, No. 12, pp 3789-3793 (1990)).
To open this barrier layer, two general techniques are currently employed. The first and more refined technique involves disruption or dissolution of the barrier layer by passing a current through the overlayer. This dissolvable material layer, preferably a thin metal foil, is oxidized galvanostatically and dissolved into the infusate solution, thereby opening the micropores for flow of the infusate therethrough. The second technique employed to "open" the micropores generally involves an overlayer of a polymeric based barrier material which spans the micropores and is impermeable to the infusate. In general, a gas is generated through electrolysis of the infusate on the electrode behind the polymer membrane which ruptures the polymer membrane, thereby uncovering the micropores. Because the electrochemistry is carried in the medicament or fluid, the infusate is contaminated. Unpredictable chemical reactions or electrochemical reactions could occur resulting in toxic products which would be infused into the recipient. The dispensed drug, for example, could be undesirable modified. Moreover, since the infusate must flow through the micropores of the membrane, the flow rate cannot accurately be controlled without careful consideration of the infusate fluid properties (i.e., bulk viscosity), the size of the micropores, and the area of disruption.
None of the foregoing references is believed to disclose the present invention as claimed and is not presumed to be prior art. The references are offered for the purpose of background information.